1. Field of the Invention
The present invention relates generally to the fields of cardiac muscle disorders and diseases. More particularly, the present invention relates to ryanodine receptor inhibitors and uses thereof for the treatment and prevention of conditions associated with extracellular calcium imbalance in cardiac muscle. The ryanodine receptor inhibitors of the present invention may serve as, for example, anti-arrhythmia agents. The ryanodine receptor inhibitors may also have reduced β-blocking activity.
2. Description of Related Art
Heart failure is a common, progressive and often fatal cardiac condition. Heart failure is responsible for millions of hospitalizations and over 300,000 deaths in the U.S. and over a million in Western countries annually, resulting in an enormous impact on public health. A leading cause of death in patients with heart failure is arrhythmia. The primary therapeutic strategy over the last several decades has been to suppress arrhythmias by the use of anti-arrhythmic drugs. Gheorghiade and Eichhorn, 2001. There are currently several types of drugs available on the market to treat various types of arrhythmias.
Of a number of anti-arrhythmic drugs used over the past several decades, β-blockers are the only class of anti-arrhythmic drugs proven to have significant survival benefits, and have become the most widely used drugs for the treatment of heart failure and cardiac arrhythmias. Foody et al., 2002. Although β-blockers have revolutionized the treatment of patients with these diseases, the absolute benefit of β-blocker treatment is low (˜7% absolute reduction in all-cause mortality). Miller, 2003. Clearly, there is a need in the art for new anti-arrhythmic drugs with better efficacy.